Specialized features of iodine metabolism in thyroid include iodide transport across the basal membrane, iodide efflux into the follicular lumen, and iodination of thyroglobulin. The process is regulated by TSH and other hormones, as well as by iodine. These studies are integral part of understanding thyroid hormone synthesis. Signal systems important in regulation of iodide transport and metabolism were developed over several years and used thyroid cells in culture. These studies show that iodide transport is regulated by cAMP and calcium/phospholipid pathways. Further studies of the iodide transport in FRTL-5 cells confirmed and extended studies that characterized iodide transport in intact tissues. Stilbenes, agents that interact with band 3, also specifically effected the transport of iodide by the thyroid. Band 3, the major integral membrane protein of mammalian erythrocytes is specifically effected by stilbenes. Band 3 functions to exchange internal bicarbonate for external chloride. Studying this function in the laboratory and using a cDNA probe to murine band 3, several cDNA clones were isolated using expression libraries made from FRTL-5 cells. Using the clones to transform cells that normally do not transport iodide, present studies transfect FRTL-5 clones into COS-7 cells to address their role in iodide transport, a role previously suggested by studies showing effects of stilbenes on iodide transport in the thyroid. Studies of goiter are completed. These studies show that in addition to low-iodinated thyroglobulin, albumin and hemoglobin are prominent proteins found in goiter tissues. The thyroid, as a site of synthesis of serum-proteins, has been addressed using mRNA from goiter tissues. Goiter from a patient with congenital goiter had an unexpected finding showing an absence of sialyltransferase activity necessary to sialylate thyroglobulin. This project has opened up a new opportunity to address tissue specific glycosyltransferase activity and function, and its potential hormonal regulation in the thyroid.